ML29255 Neoadjuvant Vemurafenib and Cobimetinib Melanoma

Launched by INOVA HEALTH CARE SERVICES · Dec 22, 2016

Keywords

ClinConnect Summary

Vemurafenib and cobimetinib are FDA-approved drugs to treat advanced melanoma that has a mutated (changed) form of a cell protein called BRAF (BRAF V600 mutation). The purpose of this study is to determine if vemurafenib and cobimetinib can be safely given to patients with this type of melanoma to shrink it before surgery. This research is being done because patients with melanoma spread to lymph node have high chance of melanoma recurrence even after lymph node removal surgery, and currently there is no approved medicine to use for patients with BRAF V600 mutant melanoma before lymph node ...

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Eligibility criteria

• Patients will be included in the study based on the following criteria:
• • Signed informed consent
• • Histologically confirmed, palpable, regional lymph node metastatic melanoma ≥ 1.5cm (stage IIIB-C; N1b-3) either at initial presentation or at regional lymph node recurrence considered surgically resectable at baseline by the treating medical oncologist and surgical oncologist
• • Patients with intransit or satellite metastases with lymph node involvement are allowed if considered surgically resectable at baseline
• • Measurable disease per RECIST 1.1
• • Melanoma must be documented to contain a BRAFV600 mutation by a CLIA approved laboratory
• • No evidence of distant metastasis
• • Age ≥ 18 years
• • ECOG performance status ≤1
• * Adequate bone marrow function as indicated by the following:
• • ANC greater than 1500/µL
• • Platelets ≥ 100,000/µL
• • Hemoglobin greater than 9 g/dL
• • Adequate renal function, as indicated by creatinine ≤1.5 x the upper limit of normal (ULN)
• • Adequate liver function, as indicated by bilirubin ≤1.5 x ULN
• • AST or ALT less than 3 x ULN (patients with documented liver metastases: AST and/or ALT ≤5 x ULN)
• • Able to swallow pills
• • Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year.
• • Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
• • Willing and able to undergo biopsy for research purposes
• • Willing and able to sign informed consent
• Exclusion Criteria:
• • Had prior radiotherapy at lymph node basin
• • Prior treatment with BRAF inhibitor or MEK inhibitor
• • Active infection
• • Pregnant, lactating or breast feeding women
• • Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• • History of malabsorption or other condition that would interfere with absorption of vemurafenib or cobimetinib
• • Any underlying medical or psychiatric condition, which in the opinion of the Investigator will make the administration of vemurafenib and cobimetinib hazardous
• • Unwillingness or inability to comply with study and follow-up procedures.
• * The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment:
• • St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer)
• • Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor)